LNP023 hydrochloride is an orally bioavailable, highly potent, and highly selective inhibitor of factor B. LNP023 exhibits direct, reversible, and high-affinity binding to human factor B, with a KD of 7.9 nM.
体内研究
LNP023 (20-180 mg/kg; oral administration) prevents KRN (150 μL)-induced arthritis in mice. It is efficacious when administered prophylactically or therapeutically in an experimental model of membranous nephropathy in rats [2].
LNP023 demonstrates moderate half-lives (T1/2; Wistar Han rats: 3.4 h, beagle dogs: 5.5 h) and Cmax values (Wistar Han rats: 410 nM, beagle dogs: 2200 nM) after oral dosing (rats: 30 mg/kg, dogs: 10 mg/kg)[3].
LNP023 shows terminal elimination half-lives (T1/2; Wistar Han rats: 7 h, beagle dogs: 5.6 h) resulting from high plasma clearance rates (8 mL/min/kg for rats and 2 mL/min/kg for dogs) and substantial volumes of distribution (2.3 L/kg for rats and 0.6 L/kg for dogs) after intravenous administration (rats: 1.0 mg/kg, dogs: 0.1 mg/kg)[3].
体外研究
LNP023 exhibits potent inhibition of membrane attack complex (MAC) formation induced by the alternative complement pathway (AP) in 50% human serum, with an IC50 value of 130 nM [2].
LNP023 demonstrates outstanding selectivity compared to other proteases, with IC50 values exceeding 30 μM across a panel of 41 human proteases, including the AP protein factor D (>100 μM) [3].
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